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Jumat, 05 Juli 2013

CHOLESTEROL

Cholesterol is a lipid (fat) which is produced by the liver. Cholesterol is vital for normal body function. Every cell in our body has cholesterol in its outer layer.

Cholesterol is a waxy steroid and is transported in the blood plasma of all animals. It is the main sterol synthesized by animals - small amounts are also synthesized in plants and fungi. A sterol is a steroid sub-group.
Cholesterol levels among US adults today are generally higher than in all other industrial nations. During the 1990s there was some concern about cholesterol levels in American children. According to the CDC (Centers for Disease Control and Prevention), nearly 1 in every 10 children/adolescents in the USA has elevated total cholesterol levels; and this was after concentrations had dropped over a 20-year period.

The function of cholesterol
Cholesterol is required to build and maintain membranes; it modulates membrane fluidity over the range of physiological temperatures. The hydroxyl group on cholesterol interacts with the polar head groups of the membrane phospholipids and sphingolipids, while the bulky steroid and the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty-acid chain of the other lipids. Through the interaction with the phospholipid fatty-acid chains, cholesterol increases membrane packing, which reduces membrane fluidity.[10] The structure of the tetracyclic ring of cholesterol contributes to the decreased fluidity of the cell membrane as the molecule is in a trans conformation making all but the side chain of cholesterol rigid and planar. In this structural role, cholesterol reduces the permeability of the plasma membrane to neutral solutes, protons, (positive hydrogen ions) and sodium ions.

Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction. Cholesterol is essential for the structure and function of invaginated caveolae and clathrin-coated pits, including caveola-dependent and clathrin-dependent endocytosis. The role of cholesterol in such endocytosis can be investigated by using methyl beta cyclodextrin (MβCD) to remove cholesterol from the plasma membrane. Recently, cholesterol has also been implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane. Lipid raft formation brings receptor proteins in close proximity with high concentrations of second messenger molecules. In many neurons, a myelin sheath, rich in cholesterol, since it is derived from compacted layers of Schwann cell membrane, provides insulation for more efficient conduction of impulses.

Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver, cholesterol is converted to bile, which is then stored in the gallbladder. Bile contains bile salts, which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble vitamins, A, D, E, and K. Cholesterol is an important precursor molecule for the synthesis of vitamin D and the steroid hormones, including the adrenal gland hormones cortisol and aldosterone, as well as the sex hormones progesterone, estrogens, and testosterone, and their derivatives. Some research indicates cholesterol may act as an antioxidant.

There are three main types of lipoproteins
Cholesterol is carried in the blood by molecules called lipoproteins. A lipoprotein is any complex or compound containing both lipid (fat) and protein. The three main types are:
• LDL (low density lipoprotein) - people often refer to it as bad cholesterol. LDL carries cholesterol from the liver to cells. If too much is carried, too much for the cells to use, there can be a harmful buildup of LDL. This lipoprotein can increase the risk of arterial disease if levels rise too high. Most human blood contains approximately 70% LDL - this may vary, depending on the person.

• HDL (high density lipoprotein) - people often refer to it as good cholesterol. Experts say HDL prevents arterial disease. HDL does the opposite of LDL - HDL takes the cholesterol away from the cells and back to the liver. In the liver it is either broken down or expelled from the body as waste.

• Triglycerides - these are the chemical forms in which most fat exists in the body, as well as in food. They are present in blood plasma. Triglycerides, in association with cholesterol, form the plasma lipids (blood fat). Triglycerides in plasma originate either from fats in our food, or are made in the body from other energy sources, such as carbohydrates. Calories we consume but are not used immediately by our tissues are converted into triglycerides and stored in fat cells. When your body needs energy and there is no food as an energy source, triglycerides will be released from fat cells and used as energy - hormones control this process.

Increase Our HDL Levels
• Aerobic exercise. Many people don't like to hear it, but regular aerobic exercise (any exercise, such as walking, jogging or bike riding, that raises your heart rate for 20 to 30 minutes at a time) may be the most effective way to increase HDL levels. Recent evidence suggests that the duration of exercise, rather than the intensity, is the more important factor in raising HDL choleserol. But any aerobic exercise helps.
• Lose weight. Obesity results not only in increased LDL cholesterol, but also in reduced HDL cholesterol. If you are overweight, reducing your weight should increase your HDL levels. This is especially important if your excess weight is stored in your abdominal area; your waist-to-hip ratio is particularly important in determining whether you ought to concentrate on weight loss.
• Stop smoking. If you smoke, giving up tobacco will result in an increase in HDL levels. (This is the only advantage I can think of that smokers have over non-smokers -- it gives them something else to do that will raise their HDL.)
• Cut out the trans fatty acids. Trans fatty acids are currently present in many of your favorite prepared foods -- anything in which the nutrition label reads "partially hydrogenated vegetable oils" -- so eliminating them from the diet is not a trivial task. But trans fatty acids not only increase LDL cholesterol levels, they also reduce HDL cholesterol levels. Removing them from your diet will almost certainly result in a measurable increase in HDL levels. Click here for a quick and easy review of trans fatty acids and the heart.
• Alcohol. With apologies to the American Heart Association, which discourages doctors from telling their patients about the advantages of alcohol: one or two drinks per day can significantly increase HDL levels. More than one or two drinks per day, one hastens to add, can lead to substantial health problems including heart failure -- and there are individuals who will develop such problems even when limiting their alcohol intake to one or two drinks per day. Click here for a quick and easy review of alcohol and the heart.
• Increase the monounsaturated fats in your diet. Monounsaturated fats such as canola oil, avocado oil, or olive oil and in the fats found in peanut butter can increase HDL cholesterol levels without increasing the total cholesterol.
• Add soluble fiber to your diet. Soluble fibers are found in oats, fruits, vegetables, and legumes, and result in both a reduction in LDL cholesterol and an increase HDL cholesterol. For best results, at least two servings a day should be used.
• Other dietary means to increasing HDL. Cranberry juice has been shown to increase HDL levels. Fish and other foods containing omega-3 fatty acids can also increase HDL levels. In postmenopausal women (but not, apparently, in men or pre-menopausal women) calcium supplementation can increase HDL levels.

Decrease LDL Without Drugs
Joseph Keenan, a cardiology researcher and professor emeritus at the University of Minnesota, has a love-hate relationship with statins. On the one hand, he prescribes them to many patients. On the other, he can't use them to control his own dangerously high cholesterol. Like many of the 25 percent or so of patients prescribed statins who abandon them within six months, Keenan has had unpleasant side effects, such as muscle spasms, and blood tests indicate muscle damage. "It came as a shock," he says of finding out he'd have to do without his Lipitor.
What recourse do people like Keenan have? Some doctors, such as Steven Nissen of the Cleveland Clinic, are so convinced of statins' lifesaving power that they first require patients to try all six before considering them intolerant. Next, patients might try a nonstatin drug such as Zetia, which lowers cholesterol by inhibiting its absorption in the intestine. But there are other weapons besides drugs in the cholesterol wars. For those intolerant of statins—and for people taking them as well—the following strategies can help defeat unhealthy cholesterol.
• Diet. The foundation of any cholesterol-lowering regimen is a balanced diet. That doesn't mean you have to buy only products whose labels scream "low cholesterol." In fact, says Christopher Gardner, a researcher at Stanford University who specializes in nutrition, a varied diet that emphasizes plants, fish, legumes, whole grains, and fruits is significantly better at lowering problematic cholesterol than a more conventional diet of prepared foods equally low in saturated fats and cholesterol. Why? Components of plant-based diets actively interact to improve cholesterol profiles, he suggests. That said, you'll still want to limit your intake of red meat, eggs, and cheese.
The so-called Mediterranean diet, the dash (Dietary Approaches to Stop Hypertension) diet, and the Ornish Diet (which is particularly low in meat and dairy) are variations on this approach. One study found that a balanced diet did just as well as a statin at reducing bad cholesterol. Dean Ornish, the founder of the Preventive Medicine Research Institute in Sausalito, Calif., has shown that his multipronged approach (diet, exercise, stress reduction, and social support), while not easy to maintain, can lower LDL by nearly 40 percent and even cause plaques in arteries to shrink—which not even statins have been proven to do.
• Exercise. Regular exercise is also critical. Some studies show that regular aerobic exercise for a period of about 12 weeks can modestly increase beneficial HDL cholesterol—between 5 and 10 percent, and more for some people. Your triglyceride level and blood pressure should respond, too. Shoot for at least 30 minutes of moderate aerobic exercise five to seven days a week.
• Supplements. Natural food stores and the Internet are awash with products claiming to improve cholesterol profiles. For most, there is little or no evidence of an effect on cholesterol levels (though some—Omega-3 fatty acids, for example—have not been studied rigorously enough to say definitely that they don't work).
Notable exceptions worth exploring include niacin, plant sterols, and soluble fiber supplements. Though niacin can raise blood sugar and cause flushing, a daily dose can raise HDL levels by 15 to 35 percent and lower LDL levels by about 20 percent. Niacin has a risk of side effects, however, especially when combined with a statin. A daily serving of plant sterols (about 2 grams), in fortified foods such as margarine, orange juice, and rice milk, can also lower LDL by about 15 percent. Eating plenty of soluble fiber, which occurs naturally in products such as oats, nuts, flax, and psyllium husk and in dietary supplements such as Metamucil, can also drop LDL. Red rice yeast, a popular dietary supplement, also works. But be warned that it contains lovastatin, the active ingredient in Mevacor, a prescription statin, and is "essentially an unregulated statin," says Robert Vogel, a cardiologist at the University of Maryland.
Lifestyle interventions often don't work nearly as well as a statin can. Exercise, a better diet, and supplements can generally reduce bad cholesterol by 20 to 40 percent, compared with 60 to 70 percent for statins. But Keenan estimates that 70 percent of people with problematic cholesterol levels could gain control with lifestyle changes alone. He has. His LDL levels are down by about 60 percent thanks to diet, exercise, niacin and other supplements. That's as good a job, he says, as Lipitor did.

Symptoms of high cholesterol (hypercholesterolaemia)
Symptoms of high cholesterol do not exist alone in a way a patient or doctor can identify by touch or sight. Symptoms of high cholesterol are revealed if you have the symptoms of atherosclerosis, a common consequence of having high cholesterol levels. These can include:
• Narrowed coronary arteries in the heart (angina)
• Leg pain when exercising - this is because the arteries that supply the legs have narrowed.
• Blood clots and ruptured blood vessels - these can cause a stroke or TIA (mini-stroke).

Ruptured plaques - this can lead to coronary thrombosis (a clot forming in one of the arteries that delivers blood to the heart). If this causes significant damage to heart muscle it could cause heart failure.

Xanthomas - thick yellow patches on the skin, especially around the eyes. They are, in fact, deposits of cholesterol. This is commonly seen among people who have inherited high cholesterol susceptibility (familial or inherited hypercholesterolaemia).

Causes of high cholesterol
Lifestyle causes
• Nutrition - although some foods contain cholesterol, such as eggs, kidneys, eggs and some seafoods, dietary cholesterol does not have much of an impact in human blood cholesterol levels. However, saturated fats do! Foods high in saturated fats include red meat, some pies, sausages, hard cheese, lard, pastry, cakes, most biscuits, and cream (there are many more).

• Sedentary lifestyle - people who do not exercise and spend most of their time sitting/lying down have significantly higher levels of LDL (bad cholesterol) and lower levels of HDL (good cholesterol).

• Bodyweight - people who are overweight/obese are much more likely to have higher LDL levels and lower HDL levels, compared to people who are of normal weight.

• Smoking - this can have quite a considerable effect on LDL levels.

• Alcohol - people who consume too much alcohol regularly, generally have much higher levels of LDL and much lower levels of HDL, compared to people who abstain or those who drink in moderation.

High cholesterol levels can cause:
Atherosclerosis - narrowing of the arteries.

• Higher coronary heart disease risk - an abnormality of the arteries that supply blood and oxygen to the heart.

• Heart attack - occurs when the supply of blood and oxygen to an area of heart muscle is blocked, usually by a clot in a coronary artery. This causes your heart muscle to die.

• Angina - chest pain or discomfort that occurs when your heart muscle does not get enough blood. Other cardiovascular conditions - diseases of the heart and blood vessels.

Stroke and mini-stroke - occurs when a blood clot blocks an artery or vein, interrupting the flow to an area of the brain. Can also occur when a blood vessel breaks. Brain cells begin to die.

If both blood cholesterol and triglyceride levels are high, the risk of developing coronary heart disease rises significantly.
The treatments for high cholesterol?
Lifestyle

Most people, especially those whose only risk factor has been lifestyle, can generally get their cholesterol and triglyceride levels back to normal by:
Doing plenty of exercise (check with your doctor)
Eating plenty of fruits, vegetables, whole grains, oats, good quality fats
Avoiding foods with saturated fats
Getting plenty of sleep (8 hours each night)
Bringing your bodyweight back to normal
Avoiding alcohol
Stopping smoking
Many experts say that people who are at high risk of developing cardiovascular disease will not lower their risk just by altering their diet. Nevertheless, a healthy diet will have numerous health benefits.
Cholesterol-controlling medications

If your cholesterol levels are still high after doing everything mentioned above, your doctor may prescribe a cholesterol-lowering drug. They may include the following:

• Statins (HMG-CoA reductase inhibitors) - these block an enzyme in your liver that produces cholesterol. The aim here is to reduce your cholesterol levels to under 4 mmol/liter and under 2 mmol/liter for your LDL. Statins are useful for the treatment and prevention of atherosclerosis. Side effects can include constipation, headaches, abdominal pain, and diarrhea. Atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin are examples of statins.

• Aspirin - this should not be given to patients under 16 years of age.

• Drugs to lower triglyceride levels - these are fibric acid derivatives and include gemfibrozil, fenofibrate and clofibrate.

• Niacin - this is a B vitamin that exists in various foods. You can only get very high doses with a doctor's prescription. Niacin brings down both LDL and HDL levels. Side effects might include itching, headaches, hot flashes (UK: flushes), and tingling (mostly very mild if they do occur).

In some cases cholesterol absorption inhibitors (ezetimibe) and bile-acid sequestrants may be prescribed. They have more side effects and require considerable patient education to achieve compliance (to make sure drugs are taken according to instruction).

Statins (or HMG-CoA reductase inhibitors) are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases,[1] and statins are therefore used in the prevention of these diseases. Research has found that statins are most effective for treating cardiovascular disease (CVD) (secondary prevention), with questionable benefit in those without previous CVD, but with elevated cholesterol levels.[2][3] Statins have rare but severe adverse effects, particularly muscle damage, and some doctors believe they are overprescribed.